Endoscope-Assisted Extracapsular Resection of Benign Parotid Tumors Via Temporal and Retroauricular Approach.

OBJECTIVE: To evaluate the feasibility of endoscope-assisted extracapsular resection of benign parotid tumors via temporal and retroauricular approach. MATERIALS AND METHODS: A total of 12 patients with parotid gland tumors had endoscope-assisted extracapsular resection performed via temporal and retroauricular approach (4 versus 8) between January 2018 and January 2019. RESULTS: All tumors were benign with a median diameter of 2.32 ± 0.49 cm. The mean length of the skin incision was 3.5 ±0.35 cm. The mean operating time 86.7 ± 10.8 minutes. The median blood loss was 30.4 ± 5.94 ml. The median volume of drainage was 27.1 ± 8.88 ml and the duration of drainage was 2 ± 0.71 days. The mean aesthetics scoring assigned by patients was 9.67 ± 0.51. Two patients had numbness of the earlobe and 1 patient developed a transient salivary sialocele. No facial nerve paresis was observed and no tumor recurrence occurred during the follow-up period. CONCLUSIONS: The minimally invasive endoscope-assisted extracapsular resection of benign parotid tumors provide both a safe and reliable technique for benign parotid tumors with excellent cosmetic results.

Repression of FBXW7 by HES5 contributes to inactivation of the TGF-ß signaling pathway and alleviation of endometriosis.

Endometriosis (EMS) is a gynecologic disorder associated with infertility and characterized by the endometrial-type mucosa outside the uterine cavity. Currently available treatment modalities are limited to undesirable effects. Thus, in the present study, we sought to study the pathogenesis mechanism of EMS. For this purpose, the ectopic and eutopic endometrial tissues were resected from 86 patients with EMS and 54 infertile patients without EMS, respectively. The regulatory mechanism among HES family bHLH transcription factor 5 (HES5), transforming growth factor-beta (TGF-ß)-induced factor 1 (TGIF1), F-box, and WD repeat domain containing 7 (FBXW7) was studied by performing co-immunoprecipitation, dual-luciferase reporter gene assay, and chromatin immunoprecipitation, respectively. A mouse model of EMS was established to verify the aforementioned regulatory mechanism in vivo. Upregulation of HES5 and TGIF1, as well as downregulation of FBXW7, was observed in EMS endometrial tissues and human endometrial stromal cells (hESCs), respectively. The overexpression of HES5 was found to suppress the FBXW7 transcription and TGIF1 degradation, resulting in the inactivation of the TGF-ß signaling pathway, as well as inhibition of hESC proliferation and invasion, thereby enhancing apoptosis. Results from a mouse model of EMS showed that the presence of HES5 contributed to the alleviation of EMS. Collectively, we attempted to provide a mechanistic insight into the unrecognized roles of the HES5/FBXW7 in EMS progression.

Tumor-induced osteomalacia characterized by "painful knee joint with difficulty in moving": a case report.

BACKGROUND: Tumor-related osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by severe hypophosphatemia and osteomalacia. The diagnosis of TIO can be very difficult because of its nonspecific nature of clinical manifestations. Here we reported a case of young TIO patient with "painful knee joint with difficulty in moving" to improve the clinical diagnosis and treatment levels. CASE PRESENTATION: The patient's clinical features were consistent with TIO. A tumor was successfully located in left tibial by 68Ga-DOTATATE PET/CT, and then was surgically resected. Upon pathologic assessment, the tumor was diagnosed as phosphaturia stromal tumor (PMT) with positive Vim staining. After the surgery, serum phosphate level rapidly recovered and symptoms significantly improved. CONCLUSION: TIO should be considered in patients with chronically hypophosphorus osteomalacia in the setting of no family history. Early removal of the responsible tumors is clinically essential for the treatment, and imaging examination is of great significance for tumor localization.

A Metallic Ion-Induced Self-Assembly Enabling Nanowire-Based Aerogels.

The controlled assembly of nanowires is one of the key challenges in the development of a range of functional 3D aerogels with unique physicochemical properties for practical applications. However, the deep understanding of the dynamic assemble process for fabricating nanowire aerogels remains elusive. Herein, a facile strategy is presented for the metallic ion-induced assembly of nanowires into macroscopic aerogels via a solution-based process. This method enables the interconnecting between polymer-decorated nanowires via metallic coordination, resulting in plenty of nanowire bundles with the same orientation. Besides, the coordinated binding strength of nanowires with different metallic ions is also discussed. The assembly mechanism that the metallic ions induced dynamic behavior of nanowires is revealed via molecular dynamics theoretical evaluation. These findings benefit for constructing nanowire-based aerogels with unique structural features and multi-function, which pave new opportunities for other material systems.

Mining of the Catharanthus roseus Genome Leads to Identification of a Biosynthetic Gene Cluster for Fungicidal Sesquiterpenes.

Characterization of cryptic biosynthetic gene clusters (BGCs) from microbial genomes has been proven to be a powerful approach to the discovery of new natural products. However, such a genome mining approach to the discovery of bioactive plant metabolites has been muted. The plant BGCs characterized to date encode pathways for antibiotics important in plant defense against microbial pathogens, providing a means to discover such phytoalexins by mining plant genomes. Here is reported the discovery and characterization of a minimal BGC from the medicinal plant Catharanthus roseus, consisting of an adjacent pair of genes encoding a terpene synthase (CrTPS18) and cytochrome P450 (CYP71D349). These two enzymes act sequentially, with CrTPS18 acting as a sesquiterpene synthase, producing 5-epi-jinkoheremol (1), which CYP71D349 further hydroxylates to debneyol (2). Infection studies with maize revealed that 1 and 2 exhibit more potent fungicidal activity than validamycin. Accordingly, this study demonstrates that characterization of such cryptic plant BGCs is a promising strategy for the discovery of potential agrochemical leads. Moreover, despite the observed absence of 1 and 2 in C. roseus, the observed transcriptional regulation is consistent with their differential fungicidal activity, suggesting that such conditional coexpression may be sufficient to drive BGC assembly in plants.

Protective Effect of N-Acetylcysteine Pretreatment on Acute Kidney Injury in Septic Rats.

BACKGROUND: The aim of this study is to investigate the protective effect of N-acetylcysteine (NAC) pretreatment on acute kidney injury in septic rats. METHODS: We constructed a septic rat model by cecal ligation and perforation (CLP) and assessed kidney tissue pathologic damage, renal function changes, and inflammatory factor levels. Meanwhile, we also assessed oxide and antioxidant enzyme levels in kidney tissues, observed apoptosis of kidney tissues, and evaluated mitochondrial membrane activity in renal cortical cells. RESULTS: Pretreatment of NAC significantly alleviated pathologic damage of kidney tissues in septic rats; decreased the levels of serum creatinine, blood urea nitrogen, plasma neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1; and reduced the expression of tumor necrosis factor a, interleukin [IL]-1ß, IL-6, and IL-8. Furthermore, NAC pretreatment reduced the level of protein-nitrotyrosine adducts and malondialdehyde in CLP-induced kidney tissues, while elevated the levels of superoxide dismutase, glutathione peroxidase, and catalase. Moreover, pretreatment of NAC reduced the number of apoptosis in kidney tissues induced by CLP, decreased the mRNA levels of caspase-3, caspase-9, cytochrome c, and poly ADP-ribose polymerase, and increased mitochondrial membrane activity in renal cortical cells (complex I/II/III/IV). CONCLUSIONS: NAC pretreatment has protective effects on acute kidney injury induced by CLP, and its mechanism is closely related to anti-inflammatory, antioxidation, antiapoptosis, and regulation of mitochondrial function.

[Limonoids from seeds of Azadirachta indica and their cytotoxic activity].

Eight limonoids were isolated from 95% ethanol extracts of neem(Azadirachta indica) seeds by various chromatographic methods. By comparison of their spectroscopic data with those reported in the literatures, these limonoids were determined as salannin(1), 1-detigloyl-1-isobutylsalannin(2), salannol-3-acetate(3), salannol(4), spirosendan(5), 1-detigloyloxy-3-deacetylsalannin-1-en-3-one(6), nimbin(7) and 6-deacetylnimbin(8). Compounds 2 and 5 were firstly isolated from this genus and 5 represented the only example of its type. And 6 is a new natural product. 6 showed inhibitory activity against HeLa and HL-60 cells, with IC50 of(21.61±4.37) and(27.33±5.74) µmol·L⁻¹, respectively. Both 7 and 8 mildly inhibited the growth of HeLa cells, with IC50 of (33.15±5.24) and (38.56±6.41) µmol·L⁻¹, respectively.

Differential Expression of MicroRNAs in Calcific Aortic Stenosis.

BACKGROUND: Calcific aortic stenosis (CAS) is the most common heart valve disorder. To explore the underlying mechanisms, we investigated whether key microRNAs in calcified aortic valves are differentially expressed compared to those in the non-calcified valves. METHODS: Calcified aortic valves from patients with aortic stenosis and non-calcified aortic valves (control) from patients with aortic insufficiency (n = 8 per group) were obtained during cardiac valve replacement surgery. The expression of miR-26a, miR-939, miR-374b*, miR-214, miR-16, miR-665, miR-130a, miR-193b, and miR-602 were evaluated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). MiRanda and TargetScan programs were used to predict target genes, which were verified at the levels of mRNA and protein. RESULTS: The expression of osteocalcin, osteopontin, Runx2, and osterix were significantly increased in the CAS group compared with the control group. The expression of miR-26a, miR-939, and miR-374b* were significantly decreased in the CAS group compared with those in the control group (p < 0.05 and p < 0.01, respectively), and the expression of miR-214 was significantly up-regulated in the CAS group compared with that in the control group (p < 0.01). No significant differences in the expression of miR-16, miR-665, miR-130a, miR-193b, and miR602 were observed between these two groups. TWIST1 was confirmed as a target for miR-214 and expression was decreased in the CAS group compared with that in the control group. CONCLUSIONS: MiR-26a, miR-939, and miR-374b* expression was decreased and miR-214 was increased in the calcified aortic valves of CAS patients. miR-214 may promote aortic valve calcification by repressing TWIST1 expression.

In Situ Loading of Drugs into Mesoporous Silica SBA-15.

In a new strategy for loading drugs into mesoporous silica, a hydrophilic (heparin) or hydrophobic drug (ibuprofen) is encapsulated directly in a one-pot synthesis by evaporation-induced self-assembly. In situ drug loading significantly cuts down the preparation time and dramatically increases the loaded amount and released fraction of the drug, and appropriate drug additives favor a mesoporous structure of the vessels. Drug loading was verified by FTIR spectroscopy and release tests, which revealed much longer release with a larger amount of heparin or ibuprofen compared to postloaded SBA-15. Besides, the in vitro anticoagulation properties of the released heparin and the biocompatibility of the vessels were carefully assessed, including activated partial thromboplastin time, thrombin time, hemolysis, platelet adhesion experiments, and the morphologies of red blood cells. A concept of new drug-release agents with soft core and hard shell is proposed and offers guidance for the design of novel drug-delivery systems.

Prospects of Robot-Assisted Mandibular Reconstruction with Fibula Flap: Comparison with a Computer-Assisted Navigation System and Freehand Technique.

Background Function and aesthetics have a significant impact on the quality of life in patients undergoing mandibular reconstructive surgery, but achieving satisfactory results remain challenging. The aim of the study is to investigate the feasibility and accuracy of robot-assisted mandibular reconstruction with fibula flap in comparison to that with a computer-assisted navigation system and the freehand technique. Methods Experimental procedures (15 phantom studies and 6 animal experiments) were performed with a custom three-arm robotic system automatically, under the guidance of a computer-assisted navigation system, and by the freehand technique, respectively. The accuracy of the reconstruction was assessed by comparison between the preoperative and postoperative three-dimensional surface virtual models. Results All procedures were successfully performed. In the phantom study, the mean deviation of the fibula implant was 1.221, 1.581, and 2.313 mm, respectively, with the robotic system, the navigation system, and the freehand technique; in the animal experiment the corresponding figures were 1.7697, 1.7847, and 2.0815 mm, respectively. The mean deviation of the proximal mandibular ramus was 1.0420, 1.0532, 1.8800 mm with the robotic system, computer-assisted navigation system, and freehand technique, respectively, and the mean deviation of the distal mandibular segment was 1.1645, 2.7198, and 2.8445 mm, respectively. Conclusions The robotic system is feasible, efficient, and reliable for mandibular reconstruction. The accuracy of the fibula implant orientation with the robotic system was comparable to that with navigation system and superior to that with the freehand technique.

Prognostic significance of B7-H3 expression in patients with colorectal cancer: A meta-analysis.

OBJECTIVE: The co-stimulatory molecule B7-H3 plays an important role in prognosis of several malignancies. However, its prognostic value in clinic in patient with colorectal cancer (CRC) is still controversial. This meta-analysis evaluated the relationship between B7-H3 expression and the outcomes of CRC patients. METHODS: PubMed, Google Scholar, Embase, CNKI and Wanfang database were searched for the studies on the relationship between the expression of B7-H3 and prognosis of CRC patients. Pooled odds ratios (ORs) analysis with 95% confidence interval (95% CIs) for lymph node metastasis, 24-month overall survival and 72-month overall survival were performed mainly using Review Manager 5.0. RESULTS: Six articles including 1,202 total CRC cases were included for the meta-analysis. Pooled analysis with fixed-effects model showed that B7-H3 expression had no relationship with lymphatic metastasis in CRC patients (Fixed-effects, OR= 1.18; 95 % CI:0.87-1.61, P=0.28). However, B7-H3 expression was associated with 24-month overall survival (Fixed-effects, OR=0.48, 95% CI:0.32-0.74, P<0.001) and 72-month overall survival (Fixed-effects, OR = 0.61, 95% CI: 0.43-0.85, P< 0.01) in CRC patients. CONCLUSION: The co-stimulatory molecule B7-H3 expression is negatively associated with lymph node metastasis in CRC. However, B7-H3 detection might be a feasible and effective means to predict the prognosis in CRC patients.

Thrombocytopenia as a predictor of severe acute kidney injury in patients with heat stroke.

BACKGROUND: Abnormalities of blood system often occur several days before acute kidney injury (AKI) in patients with heat stroke (HS). We aimed to investigate the prevalence and prognostic value of the early hematological markers in patients with AKI induced by HS. METHODS: In a retrospective cohort study, we analyzed the case records of 176 patients with HS and evaluated the hematological markers for early prediction and risk classification in the patients with AKI. RESULTS: Of 176, 103 (58%) HS cases developed AKI, and men comprised more than half (75%) of the sample population. The nadir platelet count significantly correlated with the levels of peak serum creatinine (r = -0.608, p < 0.01) and blood urea nitrogen (r = -0.546, p < 0.01), and the length of hospital stay (r = -0.393, p < 0.01). The areas under the receiver operating characteristic curves (AU-ROC) indicated the prognostic accuracy of hematological markers, AU-ROC was significantly higher with the nadir platelet count than that with the admission platelet count (AU-ROC of the nadir platelet: 0.73; 95% CI: 0.67-0.82; vs. AU-ROC of the admission platelet: 0.67; 95% CI: 0.59-0.75; p < 0.01). Multiple logistic regression results indicated that the nadir platelet count (adjusted ORs: 37.92; 95% CI: 2.18-87.21; p < 0.01) was independent predictor of AKI in HS. CONCLUSION: The high mortality observed in HS complicated with AKI, and among the various hematological parameters assessed, thrombocytopenia is associated with AKI induced by HS independently.

Ectopic trypsin in the myocardium promotes dilated cardiomyopathy after influenza A virus infection.

We have previously reported that ectopic trypsin in the myocardium triggers acute myocarditis after influenza A virus (IAV) infection. As myocarditis is a common precursor to dilated cardiomyopathy (DCM), the aim of the present study was to investigate the influence of trypsin on the progression of DCM after IAV infection. IAV-infected mice treated with saline or trypsin inhibitor were euthanized on days 0, 9, 20, 40 and 60 postinfection. Trypsin expression colocalized with myocardial inflammatory loci and IAV-induced myocarditis peaked on day 9 postinfection and alleviated by day 20 but persisted until day 60 postinfection, even though replication of IAV was not detected from day 20 postinfection. Similar time courses were observed for the activation of pro-matrix metalloproteinase (pro-MMP)-9 and expression of the proinflammatory cytokines IL-6, IL-1ß, and TNF-α. Degradation of collagen type I, proliferation of ventricular interstitial collagen, and expression of collagen type I and III mRNA increased significantly during acute and chronic phases; collagen type III mRNA increased more significantly than collagen type I mRNA. Cardiac function progressively deteriorated with progressive left ventricular dilation. The trypsin inhibitor aprotinin suppressed pro-MMP-9 activation and cytokine release, alleviated myocardial inflammation, and restored collagen metabolism during acute and chronic phases of myocarditis. This effectively prevented ventricular dilation and improved cardiac function. These results suggest that ectopic trypsin in the myocardium promoted DCM through chronic activation of pro-MMP-9, persistent induction of cytokines, and mediation of collagen remodeling. Pharmacological inhibition of trypsin activity might be a promising approach for the prevention of viral cardiomyopathy.

Comparative effects of recombinant human brain natriuretic peptide and dobutamine on acute decompensated heart failure patients with different blood BNP levels.

BACKGROUND: Recombinant human B-type natriuretic peptide (rhBNP) has been indicated for the treatment of acute decompensated heart failure (ADHF). However, the therapeutic efficacy of intravenous rhBNP is not always satisfactory in patients with extremely high blood BNP levels. In this study, we evaluated the effects of rhBNP on patients with different BNP levels. METHODS: One hundred and five patients with ADHF whose left ventricular ejection fraction (LVEF) was <40%, were assigned to a high BNP group (BNP ≤ 3000 pg/mL) or an extra-high BNP group (BNP > 3000 pg/mL) , depending on their admission plasma BNP levels. Each group was then subdivided into rhBNP or dobutamine subgroups according to intravenous administration with either rhBNP or dobutamine for 24-72h. In the high BNP group, 58 patients were randomized to subgroup rhBNP (n = 28) and subgroup dobutamine (n = 30). In the extra-high BNP group, 47 patients were randomized to subgroup rhBNP (n = 24) and subgroup dobutamine (n = 23). The effects of rhBNP and dobutamine on patients in the high and extra-high BNP groups were compared. RESULTS: In the high BNP group, rhBNP was more efficient than dobutamine at improving NYHA classification (P < 0.05), decreasing plasma BNP levels (P < 0.05), increasing LVEF (P < 0.05), and reducing hospital length of stay (P < 0.05). However, rhBNP displayed no superior therapeutic efficacy to dobutamine in the extra-high BNP group. Adverse cardiovascular events in patients treated with rhBNP were similar to adverse events in patients treated with dobutamine in both the high and extra-high BNP groups. CONCLUSIONS: rhBNP was more efficient than dobutamine at improving heart function in patients with ADHF when plasma BNP was ≤3000 pg/mL. However, rhBNP treatment showed no advantages over dobutamine when plasma BNP reached extremely high levels (>3000 pg/mL). TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01837849.

Urine neutrophil gelatinase-associated lipocalin in septic patients with and without acute kidney injury.

INTRODUCTION: Urine neutrophil gelatinase-associated lipocalin (uNGAL) is a rapidly emerging biomarker for early detection of acute kidney injury (AKI). We aimed to investigate the prevalence and prognostic value of the early uNGAL in patients with AKI induced by sepsis. METHODS: In this prospective cohort study, we analyzed the case records of 126 septic patients with and without AKI and evaluated the uNGAL for early prediction and risk stratification of septic patients with AKI. RESULTS: Of 126 patients analyzed, 58 (46%) developed septic AKI. Men comprised more than half (68%) of the sample population, the mean age (SD) was 57 years. The prognostic accuracy of uNGAL, as quantified by the area under the receiver-operating-characteristic curve (AU-ROC), was highest with peak uNGAL (AU-ROC: 0.86; 95% CI: 0.81-0.93), as compared with the admission uNGAL (AU-ROC: 0.81; 95% CI: 0.73-0.89). The peak uNGAL correlated with the levels of peak blood urea nitrogen (r = 0.674) and serum creatinine (r = 0.608), the length of hospital stay (r = 0.602) and weakly correlated with the number of hemodialysis sessions that each patient received during hospital stay (r = 0.405). By multivariate analysis, increased peak uNGAL remained independently associated with the development of septic AKI (odds ratio: 32.12; 95% CI: 6.21-90.37; p < 0.0001). CONCLUSIONS: uNGAL is independently associated with subsequent AKI among patients with sepsis.

[Effect of atorvastatin on exercise tolerance in patients with diastolic dysfunction and exercise-induced hypertension].

OBJECTIVE: To investigate the effect of atorvastatin on exercise tolerance in patients with diastolic dysfunction and exercise-induced hypertension. METHODS: A randomized, double-blind, placebo-controlled prospective study was performed. Sixty patients with diastolic dysfunction (mitral flow velocity E/A <1) and exercise-induced hypertension (SBP>200 mm Hg) treated with atorvastatin (20 mg q.d) or placebo for 1 year. Cardiopulmonary exercise test and exercise blood pressure measurement were performed. Plasma B-natriuretic peptide (BNP) concentration at rest and at peak exercise, plasma high sensitive-C reaction protein (hs-CRP) and endothelin (ET) concentration were determined at baseline and after treatment. RESULTS: After treatment by atorvastatin, the resting SBP, pulse pressure, the peak exercise SBP and BNP were significantly decreased; and the exercise time, metabolic equivalent, maximal oxygen uptake and anaerobic threshold were increased. All of these parameters had significant differences with baseline levels (P<0.05) and the rest pulse pressure, the peak exercise SBP and BNP, and the exercise time had significant differences compared with placebo treatment (P<0.05). Plasma concentrations of hs-CRP and ET were markedly reduced by atorvastatin treatment compared with baseline and placebo (P<0.05). No difference in above parameters was found before and after placebo treatment (P>0.05). CONCLUSION: In patients with diastolic dysfunction at rest and exercise-induced hypertension, atorvastatin can effectively reduce plasma hs-CRP and ET level, lower blood pressure and peak exercise SBP, decrease peak exercise plasma BNP concentration, and ultimately improve exercise tolerance.

[Results of 779 cases of neonatal fundus screening and risk factors for neonatal fundus diseases].

OBJECTIVE: To determine the prevalence and risk factors of retinal diseases of preterm infants and full term for newborns small gestational age born (SGA) by using wide-angle digital retinal imaging system (RetCam3). METHODS: Clinical data of 779 preterm and SGA infants whose eyes were detected by RetCam3 between January and December 2013 before discharge were studied retrospectively. RESULTS: Among the 779 infants, there were 69 cases of retinal hemorrhage (8.9%), 10 cases (1.3%) of retinopathy of prematurity (ROP), 9 cases of retinal exudative changes, 4 cases of retinal myelinated nerve fibers, 2 cases of congenita cataract, 3 cases of retinal chromatosis, 2 cases of retinal crystalline changes and 1 case of retinoblastoma. Logistic regression analysis indicated that low birth weight and gestational age and the history of oxygen inhalation were risk factors for the development of ROP and that vaginal delivery and mechanical ventilation increased the risk of retinal hemorrhage. CONCLUSIONS: Neonatal fundus diseases may be so various and harmful that early fundus screening should be carried out on high-risk infants, such as preterm and SAG infants. Preventive measures should be taken against the risk factors for fundus diseases.